This program proposes a multidisciplinary approach to examine the preclinical pharmacology of psychoactive drugs used in developmental disorders and mental retardation. While this avenue of study could apply to all classes of drugs used for central disorders, the proposal will initially focus attention on disorders such as autism and hyperkinesis. Using established procedures to evaluate the pharmacokinetics and metabolism of these classes of drugs, studies are proposed to relate blood content with pharmacological activity of the drug and to determine if drug metabolism is changed during the course of development. Because the psychoactive drugs under consideration involve long-term drug administration, preclinical studies will assess possible drug effects on animal's growth and development and will test for alterations of brain chemistry, neural development, sexual development, and ability to perform behavioral tasks. With the view that the knowledge of a drug's biochemical actions can be used to generate testable hypotheses concerning the underlying etiology of mental disorders, preclinical studies will also be designed to understand the basic actions of antipsychotic and CNS stimulant drugs. Finally, a portion of the work will be involved with examining animal models which might provide predictive screens for drugs used in hyperkinesis and in the treatment of behavioral disorders. Thus, this project should provide methods and criteria by which psychoactive drugs can be evaluated during development, and will provide methodology by which adverse and therapeutic effects of drugs can be defined.